Characterization and Implication of Prolactin Receptor Mutants in Human Breast Diseases
There is currently no known genetic disease linked to prolactin (prl) or its réceptor (prlR)
in humans. In a previous work, we have identified a new mutation of prolactin receptor that
leads to it's constitutive activation and to cell proliferation signalling cascades (i.e.
through MAP kinases).
This result suggests that PRLR mutants may have a strong physiopathological impact on breast
diseases etiology and/or development and/or evolution.
Based on this, we will pursue the identification of new PRLR mutants in various breast
diseases and continue their in vitro functional characterization and then analyse their in
vivo consequences on breast tissue samples collected within these women.
1. In a first time we wish to confirm our previous results on multiple fibroadenomas
(MFA). The current cohort will be augmented with 30 to 35 new patients each year. We
will confirm our in vitro results in vivo with tumoral and peri-tumoral tissue samples.
2. We then wish to extend this study to other rare breast pathologies (i.e. gigantomastia,
phyllodies tumors, giant fibroadenomas) and to more common ones (simple fibroadenomas)
to demonstrate a link between simple FA and MFA.
3. in a third time we will try to determinate whether a constitutive activation of PRLR
leads to enhanced occurrence of benign / malign transitions.
Time Perspective: Cross-Sectional
Sequencing of PRLR
Philippe Touraine, MD, PhD
Assistance Publique - Hôpitaux de Paris
France: Ministry of Health